Author:
Maeyama Masahiro,Tanaka Kazuhiro,Nishihara Masamitsu,Irino Yasuhiro,Shinohara Masakazu,Nagashima Hiroaki,Tanaka Hirotomo,Nakamizo Satoshi,Hashiguchi Mitsuru,Fujita Yuichi,Kohta Masaaki,Kohmura Eiji,Sasayama Takashi
Abstract
AbstractThe ketogenic diet (KD) is a high fat and low carbohydrate diet that produces ketone bodies through imitation of starvation. The combination of KD and Bevacizumab (Bev), a VEGF inhibitor, is considered to further reduce the supply of glucose to the tumor. The metabolite changes in U87 glioblastoma mouse models treated with KD and/or Bev were examined using gas chromatography-mass spectrometry. The combination therapy of KD and Bev showed a decrease in the rate of tumor growth and an increase in the survival time of mice, although KD alone did not have survival benefit. In the metabolome analysis, the pattern of changes for most amino acids are similar between tumor and brain tissues, however, some amino acids such as aspartic acid and glutamic acid were different between tumors and brain tissues. The KD enhanced the anti-tumor efficacy of Bev in a glioblastoma intracranial implantation mouse model, based on lowest levels of microvascular density (CD31) and cellular proliferation markers (Ki-67 and CCND1) in KD + Bev tumors compared to the other groups. These results suggested that KD combined with Bev may be a useful treatment strategy for patients with GBM.
Funder
the Japanese Ministry of Education, Culture, Sports, Science, and Technology
Publisher
Springer Science and Business Media LLC
Cited by
17 articles.
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